Osteoarthritis (OA) debilitates millions of people and is a tremendous burden on health care system worldwide. OA is a condition characterized by changes to the integrity of articular cartilage and subchondral bone. Articular cartilage has a layered structure which can be divided into four zones namely the superficial zone, the transitional zone, the radial zone and the zone of calcified cartilage (ZCC). Conventional MR imaging focuses on the three superficial zones of cartilage, and generally disregards the ZCC for technical reasons. The ZCC is a highly modified mineralized region of articular cartilage that forms an important interface between cartilage and bone. It is a region that may change dramatically in OA. The ZCC may be reactive and progressively calcify adjacent unmineralized cartilage, and this may contribute to subsequent cartilage thinning by increasing the gradient of force across the uncalcified cartilage, leading to further damage to the cartilage. Thus study of early and late alterations to the ZCC may be of critical importance in elucidating the structural and functional pathogenesis of OA. With minor exceptions, almost all of our knowledge about the formation, development maturation, aging, and changes in the ZCC in the setting of OA has come from the application of microscopic techniques. Noninvasive imaging and quantification of the ZCC would be a highly desirable supplement to this. CT has limited role in the imaging of cartilage and shows no evidence of the ZCC. Conventional magnetic resonance (MR) pulse sequences are unable to image the ZCC which has a very short transverse relaxation time (T2). As a consequence, the MR properties of the ZCC, such as its T2 which reflect molecular level changes in collagen structure, and T1 which has been shown to correlate with proteoglycan (PG) depletion (an early sign of OA) in the superficial zones of cartilage, are virtually unknown. In this proposal, we wish to develop both 2D and 3D dual adiabatic inversion recovery (DIR) prepared ultrashort echo time (UTE) pulse sequences with TEs as short as 8 s, which is 100-1000 times shorter than those available with conventional clinical sequences, to selectively visualize the ZCC. Two long adiabatic inversion pulses are employed to uniformly invert and null long T2 water (such as these in the more superficial zones of cartilage) and fat, respectively, in order to produce high contrast visualization of the ZCC. Secondly, we wish to develop quantitative techniques to evaluate the MR properties of the ZCC, including T1, T2*, T2 and T1 by combining DIR UTE with appropriate preparation and measurement pulses. Finally, we wish to evaluate the DIR UTE sequences both qualitatively and quantitatively for depicting lesions in the ZCC in 40 human cadaveric patella samples (5 normal patellae, 35 patellae with mild to moderate OA) using quantitative histology as a gold standard. The DIR UTE sequences may make it possible to non-invasively assess the involvement of the previously MR "invisible" ZCC in OA, provide the quantitative MR information about the role of ZCC in different phases of the disease and may allow early diagnosis of OA. PUBLIC HEALTH RELEVANCE: The goal of this project is to qualitatively and quantitatively evaluate the zone of calcified cartilage of normal human cadaveric patella specimens (n=5) and patellae with mild to moderate OA (n=35) using 2D and 3D DIR UTE sequences, and correlate the DIR UTE MR findings with quantitative histological analysis.